Olaparib Tablets as a Treatment for Ovarian Cancer Subjects With Different HRD Tumor Status

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This is a non-randomized, open-label study to assess olaparib tablets as a treatment for subjects with different homologous recombination deficiency (HRD) tumor status and with platinum-sensitive, relapsed, high-grade serous or high-grade endometrioid ovarian cancer. Subjects should have received at least 1 prior line of platinum-based chemotherapy.

Condition or disease

Intervention/treatment

Phase

Relapsed Ovarian Cancer, BRCA Mutation, Platinum Sensitivity

Drug: OLAPARIB

Phase 2

Expanded Access : An investigational treatment associated with this study has been approved for sale to the public.
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Detailed Description:

This is a Phase II, open-label, non-randomized, multi-center study assessing the efficacy and safety of olaparib tablets 300 mg (two 150 mg tablets) given orally twice daily (bid) in subjects with platinum-sensitive or partially platinum-sensitive, relapsed, high-grade serous or high-grade endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received at least 1 prior line of platinum-based chemotherapy.

The study will assess the effectiveness of olaparib tablets as measured by the objective response rate (ORR) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, in subjects with germline BRCA mutations (gBRCAm), somatic BRCA mutations (sBRCAm), or potential aberrations in homologous recombination deficiency (HRD) as determined by myChoice® HRD, as well as in subjects without identifiable HRD. This study will utilize Myriad BRACAnalysis CDx® for germline BRCA analysis and a tumor test (myChoice® HRD) for tumor BRCA analysis and HRD status. Four cohorts will be identified based upon the genetic testing described above:

Non-Randomized, Open-Label Phase II Study to Assess Olaparib Tablets as a Treatment for Subjects With Different HRD Tumor Status and With Platinum-Sensitive, Relapsed, High-Grade Serous or High-Grade Endometrioid Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer That Have Received at Least 1 Prior Line of Chemotherapy

Objective Response Rate, defined as the percentage of subjects with a best overall response of confirmed complete response (CR) or partial response (PR) [ Time Frame: From first dose up until progression, or last evaluable assessment in the absence of progression (up to 36 months) ]

To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using ORR according to RECIST v1.1 criteria (Investigator determined)

Secondary Outcome Measures :

Duration of response, for those subjects with a confirmed response of CR or PR [ Time Frame: From the date of the measurement criteria for CR or PR are first met until the date of documented progression or death in the absence of disease progression (up to 36 months) ]

To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using duration of response

CA-125 response rate, defined as the percentage of subjects with a CA-125 response according to GCIG criteria divided by the number of subjects evaluable for CA-125 response [ Time Frame: From baseline to Day 1 of each cycle and end of study treatment visit (up to 36 months) ]

To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using CA-125 response rate

Disease control rate defined as the percentage of subjects who have a best overall response of CR or PR or SD at greater than or equal to 8 weeks divided by the number of subjects in the efficacy analysis set, prior to any PD event [ Time Frame: From first treatment to greater than or equal to 8 weeks ]

To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using disease control rate (DCR). DCR is defined as the percentage of subjects with a best overall response of CR or PR (at any time up to and including the defined analysis cut-off point) or who have demonstrated stable disease (SD) for at least 8 weeks from first dose, divided by the number of subjects in the efficacy analysis set.

Progression free survival [ Time Frame: From first dose to earlier date of assessment of objective progression or death by any cause in the absence of progression (up to 36 months) ]

To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using progression free survival

Time to any progression [ Time Frame: From first dose to earlier date of CA-125 progression or RECIST v1.1 progression, or death by any cause in absence of progression (up to 36 months) ]

To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using time to any progression

Overall survival [ Time Frame: From date of first dose to date of death from any cause (up to 48 months) ]

To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using overall survival

HRD status as per HRRm gene panel assessment will be correlated with clinical outcome (ORR) for subjects enrolled in the 2 cohorts with BRCAwt (cohorts 3 and 4) [ Time Frame: At baseline ]

To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using HRRm gene panel status related to clinical outcome

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Layout table for eligibility information

Ages Eligible for Study:

18 Years to 130 Years (Adult, Older Adult)

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Provision of written signed informed consent prior to any study specific procedures;

At least 1 lesion (measurable by RECIST v1.1) that can be accurately assessed at baseline by computed tomography (CT)/magnetic resonance imaging (MRI) and is suitable for repeated assessment;

Subjects must have received at least 1 prior platinum-based line of chemotherapy for ovarian cancer. Note: There is no limit on the number of lines of chemotherapy;

Subjects must be partially-platinum-sensitive (defined as progression 6 to 12 months after the end of the last platinum-based chemotherapy) or platinum sensitive (defined as progression > 12 months after the end of the last platinum-based chemotherapy);

Subjects must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment;

ECOG performance status 0 to 1;

Subjects must have a life expectancy greater than or equal to 16 weeks;

Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on Day 1;

Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations; and

Formalin fixed, paraffin embedded tumor sample (either archival or fresh sample) from the primary or recurrent cancer must be available for central testing. If there is not written confirmation of the availability of an archived or fresh tumor sample prior to enrollment, the subject is not eligible for the study.

Exclusion Criteria:

Involvement in the planning and/or conduct of the study (applies to both AstraZeneca Representative staff and/or staff at the study site);

Previous enrollment in the present study;

Exposure to any investigational product (IP) within 30 days or 5 half-lives (whichever is longer) prior to start of study treatment;

Any previous treatment with a PARP inhibitor, including olaparib;

Subjects who have platinum-resistant or refractory disease defined as progression during or within 6 months of the last platinum-based chemotherapy;

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Supporting Materials:

Study Protocol
Statistical Analysis Plan (SAP)

Time Frame:

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Access Criteria:

When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.